Endo-SOFT: study protocol for a national multicentre randomised controlled trial - first-line surgery versus first-line assisted reproductive technologies in patients with advanced endometriosis.

INTRODUCTION

Endometriosis is a chronic, inflammatory and oestrogen-dependent disease frequently causing infertility. Assisted reproductive technologies (ART) are often required to achieve pregnancy, especially in women with advanced endometriosis. To date, there is no randomised controlled trial (RCT) exploring reproductive outcomes after first-line surgery followed by ART versus first-line ART in women with stage III-IV endometriosis. The aim in this study is to investigate if endometriosis surgery prior to ART in women with endometriosis stage III-IV and infertility results in improved reproductive outcomes compared with first-line ART.

METHODS AND ANALYSIS: A national multicentre prospective open label RCT including 350 subjects with stage III-IV endometriosis and infertility. Women aged 18-38 will be randomised 1:1 to endometriosis surgery prior to ART or first-line ART. Follow-up until 3 years from the first treatment.The primary outcome is the cumulative live birth rate 3 years after inclusion. Secondary outcomes are cumulative pregnancy rate, reproductive outcomes per in vitro fertilisation cycle, miscarriage rate, time to pregnancy and live birth, plasma progesterone levels on the day of frozen embryo transfer in hormone replacement cycles, obstetrical outcomes and complications, infections after oocyte retrieval, intraoperative and postoperative complications, pain, quality of life and cost-effectiveness.

ETHICS AND DISSEMINATION: The study protocol, patient information and informed consent are approved by Swedish Ethical Review Authority (dnr: 2024-04293-01, approved 7 October 2024, amendment, dnr: 2025-03699-02, approved 17 June 2025).An interim analysis is scheduled to ensure the safety of the interventions.The results of Endo-SOFT (Endometriosis: Surgery Or Fertility Treatment) will be published in scientific journals and are expected to influence clinical guidelines.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT07240363.